title: Stabilization of fibrin clots by activated prothrombin complex concentrate and tranexamic acid in FVIII inhibitor plasma.
abstract: Defective hemostasis in haemophilia patients with FVIII inhibitors results in a dramatic decrease in thrombin generation forming unstable fibrin clots that are susceptible to fibrinolyisis. In this study we tested whether the combination of plasma derived activated prothrombin complex concentrate (pd-aPCC) with tranexamic acid (TXA) may improve fibrin clot stability in FVIII inhibitor plasma. A microplate assay for clot lysis time was used to assess clot stability in FVIII inhibitor plasma. The effect of pd-aPCC on clot stability was first tested using the commercial FVIII inhibitor plasma. TXA (5 ~ 10 mg mL⁻¹) increased clot lysis time, but pd-aPCC (0.25 ~ 1.0 U mL⁻¹) had no effect on it. The combination of pd-aPCC and TXA significantly increased clot lysis time compared with TXA alone. The effect appeared to be limited to fibrin clot resistance to fibrinolysis, as TXA was found to have no effect on thrombin generation induced by pd-aPCC. The effect of pd-aPCC and TXA on clot stability was then tested and verified in plasma samples from ten patients with severe haemophilia A and inhibitors. The combination of TXA (10 mg mL⁻¹) and pd-aPCC (0.5 U mL⁻¹) significantly increased clot lysis time compared to TXA alone. Our results suggest that the combination of pd-aPCC with TXA improves clot stability in FVIII inhibitor plasma without additional increases in thrombin generation.
authors.affiliation: Centre for Haemostasis and Thrombosis, St Thomas' Hospital, London, UK. letian.dai@kcl.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Dai
authors.forename: D
authors.initials: D
authors.lastname: Bevan
authors.forename: S
authors.initials: S
authors.lastname: Rangarajan
authors.forename: B
authors.initials: B
authors.lastname: Sørensen
authors.forename: M
authors.initials: M
authors.lastname: Mitchell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D005342:Fibrinolysis / Q000187:drug effects*; D006467:Hemophilia A / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D014148:Tranexamic Acid / Q000494:pharmacology*
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D014148:Tranexamic Acid; D013917:Thrombin